Mannose-binding lectin and complement mediate follicular localization and enhanced immunogenicity of diverse protein nanoparticle immunogens

Benjamin J Read; Lori Won; John C Kraft; Isaac Sappington; Aereas Aung; Shengwei Wu; Julia Bals; Chengbo Chen; Kelly K Lee; Daniel Lingwood; Neil P King; Darrell J Irvine

doi:10.1016/j.celrep.2021.110217

Mannose-binding lectin and complement mediate follicular localization and enhanced immunogenicity of diverse protein nanoparticle immunogens

Cell Rep. 2022 Jan 11;38(2):110217. doi: 10.1016/j.celrep.2021.110217.

Authors

Benjamin J Read¹, Lori Won², John C Kraft³, Isaac Sappington³, Aereas Aung⁴, Shengwei Wu⁴, Julia Bals⁵, Chengbo Chen⁶, Kelly K Lee⁶, Daniel Lingwood⁵, Neil P King³, Darrell J Irvine⁷

Affiliations

¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
⁴ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁵ The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02139, USA.
⁶ Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA; Biological Physics Structure and Design Program, University of Washington, Seattle, WA 98195, USA.
⁷ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02139, USA; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: djirvine@mit.edu.

Abstract

Nanoparticle (NP) vaccine formulations promote immune responses through multiple mechanisms. We recently reported that mannose-binding lectin (MBL) triggers trafficking of glycosylated HIV Env-immunogen NPs to lymph node follicles. Here, we investigate effects of MBL and complement on NP forms of HIV and other viral antigens. MBL recognition of oligomannose on gp120 nanoparticles significantly increases antigen accumulation in lymph nodes and antigen-specific germinal center (GC) responses. MBL and complement also mediate follicular trafficking and enhance GC responses to influenza, HBV, and HPV particulate antigens. Using model protein nanoparticles bearing titrated levels of glycosylation, we determine that mannose patches at a minimal density of 2.1 × 10^-3 mannose patches/nm² are required to trigger follicular targeting, which increases with increasing glycan density up to at least ∼8.2 × 10^-3 patches/nm². Thus, innate immune recognition of glycans has a significant impact on humoral immunity, and these findings provide a framework for engineering glycan recognition to optimize vaccine efficacy.

Keywords: lymph node trafficking; mannose-binding lectin; nanoparticle; vaccine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens / metabolism
Antigens, Viral / immunology
Complement System Proteins / metabolism
Drug Delivery Systems / methods*
Female
Germinal Center / metabolism
Glycosylation
HIV-1 / drug effects
HIV-1 / immunology*
Humans
Immunity, Humoral / immunology
Male
Mannose
Mannose-Binding Lectin / immunology*
Mice
Mice, Inbred C57BL
Nanoparticle Drug Delivery System / pharmacology
Nanoparticles
Polysaccharides / metabolism

Substances

Antigens
Antigens, Viral
Mannose-Binding Lectin
Nanoparticle Drug Delivery System
Polysaccharides
Complement System Proteins
Mannose

Abstract

Publication types

MeSH terms

Substances

Grants and funding